The proton inventory technique will be rigorously evaluated as a method for determining the transition state structure for several biologically important reaction types. The influence of reaction conditions on the shape of proton inventories will be outlined. This work will allow an assessment of the technique in assigning observed solvent isotope effects in intermolecular, intramolecular, and enzymatic catalysis to specific sources. The results will provide information about the importance of proton transfers in catalysis and the factors which influence these transfers.